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Ternary polyelectrolyte/protein comp...

Tian, Li.

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Ternary polyelectrolyte/protein complex for tumor pH targeting and intracellular delivery.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Ternary polyelectrolyte/protein complex for tumor pH targeting and intracellular delivery./
作者:	Tian, Li.
面頁冊數:	239 p.
附註:	Source: Dissertation Abstracts International, Volume: 75-08(E), Section: B.
Contained By:	Dissertation Abstracts International75-08B(E).
標題:	Pharmaceutical sciences. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3617947
ISBN:	9781303858932

Ternary polyelectrolyte/protein complex for tumor pH targeting and intracellular delivery.
Tian, Li.

Ternary polyelectrolyte/protein complex for tumor pH targeting and intracellular delivery. - 239 p.

Source: Dissertation Abstracts International, Volume: 75-08(E), Section: B.

Thesis (Ph.D.)--The University of Utah, 2014.

This item is not available from ProQuest Dissertations & Theses.

The aim of these studies was to develop a tumor-targeting protein delivery system, without chemically linking the protein to the polymer carrier.

ISBN: 9781303858932Subjects--Topical Terms:

3173021
Pharmaceutical sciences.

Ternary polyelectrolyte/protein complex for tumor pH targeting and intracellular delivery.
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245 1 0 $a Ternary polyelectrolyte/protein complex for tumor pH targeting and intracellular delivery.
300 $a 239 p.
500 $a Source: Dissertation Abstracts International, Volume: 75-08(E), Section: B.
500 $a Adviser: You Han Bae.
502 $a Thesis (Ph.D.)--The University of Utah, 2014.
506 $a This item is not available from ProQuest Dissertations & Theses.
520 $a The aim of these studies was to develop a tumor-targeting protein delivery system, without chemically linking the protein to the polymer carrier.
520 $a Polyelectrolyte/protein complexes have long been studied; however, there is only limited information on their application in intracellular protein delivery, especially the protein escape from the endosome to the cytosol. Therefore, the first part of the dissertation investigates the intracellular behavior of the complexes between endosomolytic, thiol-triggered degradable polyelectrolytes and model proteins. The resultant complexes maintained the proton buffering capacity. Under cytosol-mimicking thiol-rich conditions, the sizes of reducible polymer/protein complexes increased significantly with a higher protein release, when compared with corresponding nonreducible polyelectrolyte/protein complexes. The polyelectrolyte/protein complexes showed similar cellular uptake to the corresponding proteins alone, but the reducible ones allowed more protein to escape into the cytosol from endolysosomes than the nonreducible ones. In addition, the proteins in the polyelectrolyte/protein complexes maintained their intrinsic secondary structures. The results show the potential of the designed endosomolytic, reducible polyelectrolytes for the delivery of proteins to the cytosol.
520 $a In the second part of the dissertation, sulfonamide-based polymer (PEG- block-oligosulfadimethoxine; PEG-b-OSD) was synthesized and complexed with polycation/BSA complexes. In solid tumors, extracellular pH (pHe) is lower than normal physiological pH. The OSD block of PEG-b-OSD would be charged at physiological pH and partially uncharged at tumor pHe. The results suggest a complete shield of the polycation/BSA complexes by the charged PEG-b-OSD at pH 7.4, which decreased the cellular uptake of BSA. At pH 6.6, despite the occurrence of a phase separation, low cytotoxicity was observed for the ternary complexes, together with BSA uptake by MCF7 cells. The results suggest the potential of tumor-specific targeting of protein complexes with sulfonamide-based polymer.
520 $a The Appendix describes the synthesis of a sulfonamide graft polymer, and the effect of hydrophobic modification of the polymer to its complex with short-chained polycation. The result demonstrated a faster release of the incorporated short-chained polycation at pH 6.8 when compared with pH 7.4.
520 $a These results demonstrated the feasibility of reducible polyelectrolyte in the application of intracellular protein delivery, and the promise of tumor-specific targeting of protein with sulfonamide-based delivery system.
590 $a School code: 0240.
650 4 $a Pharmaceutical sciences. $3 3173021
690 $a 0572
710 2 $a The University of Utah. $b Pharmaceutics and Pharmaceutical Chemistry. $3 3185086
773 0 $t Dissertation Abstracts International $g 75-08B(E).
790 $a 0240
791 $a Ph.D.
792 $a 2014
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3617947